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El adecuado manejo perioperatorio del dolor agudo y la elección de la técnica anestésica influyen en la incidencia de complicaciones a corto, mediano y largo plazo, encontrándose en este grupo el desarrollo de dolor crónico no oncológico (DCNO). Debido al aumento de la prevalencia de dolor crónico no oncológico y su relación con un manejo inadecuado o insuficiente del dolor agudo en el periodo perioperatorio, hemos realizado una revisión de su fisiopatología, los factores de riesgo y las técnicas preventivas que permitirían mitigar y/o disminuir su incidencia.
The adequate perioperative management of acute pain and the correct choice of the anesthetic technique influence the incidence of complications in the short, medium and long term, being in this group the development of chronic non-oncological pain (CNOP). Due to the increase in the prevalence of non-oncological chronic pain and its relation with an inadequate or insufficient management of acute pain in the perioperative period, we have carried out a review of its pathophysiology, risk factors and preventive techniques that would allow mitigating and/ordecrease its incidence.
Subject(s)
Humans , Pain, Postoperative/physiopathology , Chronic Pain/physiopathology , Pain Management , Hyperalgesia/physiopathologyABSTRACT
Objective To investigate the effect of nuclear factor erythroid 2-related factor 2(Nrf2)-autophagy pathway on the incisional pain-remifentanil-induced hyperalgesia of rat model. Methods Twenty-four male Sprague-Dawley rats were randomly allocated into three groups:saline+incisional pain group(group I),remifentanil+incisional pain group(group RI)and Nrf2 agonist t-BHQ group(group tBHQ),with 8 rats in each group.In group I and RI,normal saline at 0.1 mL/(kg· min) and remifentanilat 1 μg/(kg·min) were respectively infused into caudal vein for 60 min. Rats in group t-BHQ were injected intraperitoneally with Nrf2 agonist t-BHQ(15 mg/kg),the first time at 0.5 h before remifentanil infusion,per 12 h once,4 times in a row,the rest management was the same as group RI.Brennan incision pain model rats were constructed along with the infusions in the three groups. The thermal paw withdraw latency (PWL) and mechanical paw withdraw threshold(PWT)were measured at 24 h before the infusion(T0)and at 2 h(T1),6 h(T2),24 h(T3),48 h(T4)after the infusion. Rats were sacrificed after the tests, then the L4-6segments of signal cord were removed and the expression levels of autophagy-related proteins,microtubule associated protein 1 light chain 3Ⅱ(LC3Ⅱ),Beclin 1,Nrf2 and Nrf2 downstream molecular hemeoxygenase-1 (HO-1) were detected by Western blot assay. Results The PWT and PWL values were decreased significantly with the prolongation of the processing time in the three groups. Compared with group I, PWL and PWT values were decreased at T1-4,the expression levels of LC3Ⅱand Beclin-1 were increased while Nrf2 and HO-1 were decreased at T4in group RI (P<0.05). While compared with group RI, PWL and PWT values were increased, and the expressions of Nrf2 and HO-1 were increased, LC3Ⅱ and Beclin-1 protein were upregulated in group tBHQ (P<0.05).Conclusion The activation of Nrf2-autophagy pathway can improve the incisional pain-remifentanil induced hyperalgesia.
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<p><b>OBJECTIVE</b>To observe the impacts of electroacupuncture (EA) on microgliacytes and astrocytes of cervical spinal cord in rats with thyroid incisional pain and explore the mechanism of acupuncture anesthesia in thyroid surgery.</p><p><b>METHODS</b>Sixty Wistar male rats were randomized into a normal group, a model group, a Futu (LI 18) group, a Hegu (LI 4)-Neiguan (PC 6) group and a Zusanli (ST 36)-Yanglingquan (GB 34) group, 12 rats in each one. Except the normal group, a longitudinal incision, about 1.5 cm in length was done along the neck midline in the rats of the rest groups to prepare the model of thyroid incisional pain. In the Futu (LI 18) group, the Hegu (LI 4)-Neiguan (PC 6) group and the Zusanli (ST 36)-Yanglingquan (GB 34) group, after modeling for 4 h, 24 h and 48 h, EA was applied to bilateral "Futu" (LI 18), "Hegu" (LI 4) "Neiguan" (PC 6) and"Zusanli" (ST 36) "Yanglingquan" (GB 34) separately, once a day, continuously for 3 days. In the normal group and the model group, no any intervention was applied. The thermal radiant apparatus was used to detect the thermal pain threshold (PT). The fluorescence quantitative RT-PCR and the Western blotting (WB) were used to determine the expressions of protein and gene of microglia activation markers Iba1 and CD11b and the astrocyte specific protein marker, glial fibrillary acid protein (GFAP) in cervical spinal cord (Cto C) after intervention in the rats of each group.</p><p><b>RESULTS</b>After intervention, as compared with the normal group, in the model group, the neck PT was reduced apparently (<0.05), the expressions of Iba1 and CD11b and GFAP mRNA as well as the protein expressions in the spinal cord of Cto Cwere up-regulated apparently (<0.05,<0.01). As compared with the model group, in the Futu (LI 18) and the Hegu (LI 4)-Neiguan (PC 6) group, PT was increased significantly (both<0.05) and that did not change apparently in the Zusanli (ST 36)-Yanglingquan (GB 34) group (>0.05). In the Futu (LI 18) group, the protein and gene expressions of Iba1, CD11b and GFAP were lower than those in the model group (all<0.05). In the Hegu (LI 4)-Neiguan (PC 6) group, the expressions of Iba1 mRNA, CD11b protein, GFAP mRNA and protein were all lower apparently than those in the model group (all<0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1, CD11b and GFAP proteins were not different significantly as compared with the model group (all>0.05). In the Zusanli (ST 36)-Yanglingquan (GB 34) group, the expressions of Iba1 mRNA and CD11b mRNA and protein expressions in the spinal cord of Cto Cwere higher apparently than those in the Futu (LI 18) group (<0.01,<0.05); the expressions of Iba1 mRNA and CD11b protein expressions were higher than those in the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05); GFAP mRNA and protein expressions were higher apparently than those in the Futu (LI 18) group and the Hegu (LI 4)-Neiguan (PC 6) group (all<0.05).</p><p><b>CONCLUSIONS</b>EA at "Futu" (LI 18) or "Hegu" (LI 4), "Neiguan" (PC 6) relieves the acute neck incisional pain in the rats and its effect may be closely relevant with the down-regulation of the activities of microgliacytes and astrocytes in the spinal cords.</p>
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Objective To observe changes of motilin(MTL) levels in gastric body, duodenum and plasma in rat model of acute incisional pain.Methods A total of 156 healthy male adult SD rats,weighing 180-220 g,were randomized into two groups:control group (group C,n=78) and incisional pain group (group P,n=78),Rats in P group received incision on the right plantaris. Values of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at dif?ferent time points of 24 hours before operation (T0) and 1 hour (T1),6 hours (T2),24 hours(T3),48 hours (T4) and 72 hours (T5) after operation were measured in six rats chosen randomly from each group. Twelve rats were chosen from each group at T 0-5, and sacrificed. The MTL levels in plasma, the mucosal tissues of gastric body and duodenum were detected by ELISA. Re?sults Compared with group C, PWMT and PWTL were significantly decreased at T1-4 in group P. The MTL levels were sig?nificantly decreased in plasma and gastric body (P0.05). The plasma MTL levels were positively correlated with PWMT and PWTL (r=0.952,r=0.879,respectively,P<0.01) in P group. The MTL levels in gastric body were positively correlated with PWMT and PWTL(r=0.970,r=0.931,respectively,P<0.01) in P group. The MTL levels were neg?atively correlated with PWMT and PWTL(r=-0.991,r=-0.975,respectively,P<0.01) in duodenum in P group. Conclu?sion The MTL levels in plasma and gastric body are decreased in rat model of acute incisional pain, and increased in duo?denum.
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Objective To observe the effect of auricular-plaster therapy on non-incisional pain from post-laparoscopic surgery.Methods Sixty patients with non-incisional pains from laparoscopic surgery were divided into experimental group (n=30) and control group (n=30).The patients of control group after laparoscopic surgery were routinely given the oxygen inhalation for 6 hours and encouraged to do off-bed activity earlier.Besides the above-mentioned treatment,the patients of experimental group were additionally given auricular-plaster therapy.The patients of two groups were compared in terms of pain intensity and duration.Result The pain duration in the experimental group was significantly shorter and the pain density was significantly lower than that of the control group (bothP<0.05).Conclusion Auricular-plaster therapy can significantly reduce the duration and intensity of non-incisional pain from gynecological laparoscopy.
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Objective To investigate effects of intrathecal injection of morphine and fentanyl combined with low-dose naloxone on the pain behavior and the expression of blood motilin (MTL) in the rat model of incisional pain.Meth?ods A total of 72 healthy male Sprague-Dawley rats (weight 180-220 g), successfully intrathecally catheterized, were ran?domly divided into 6 groups (n=12 ):normal saline group (NS group), incisional pain group (P group), morphine (5μg/kg)+fentanyl (0.25μg/kg) group (MFP group), morphine+fentanyl+naloxone (0.2 ng/kg, 1 ng/kg, 5 ng/kg) group (MFPN1, MF?PN2 and MFPN3 groups). All groups except NS group were made the model of incisional pain on the right plantar surface. At 24-hours before intrathecal cathetherization (T0), 24-hours before modelling (T1), 1-hours (T2), 3-hours (T3) , 6-hours (T4), 24-hours (T5) , 48-hours (T6) and 72-hours (T7) after modelling respectively, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were detected in right hind paw in 6 rats of each group. The other 6 rats in each group were sacrificed 6-hour after operation. The plasma expression of motilin was detected by ELISA. Re?sults Compared with NS group, the PWMT was not significantly different in all time points in MFPN2 group. The values of PWTL were significantly longer at T2 and T5 in MFPN2 group than those of NS group (P0.05).Conclusion In the rat model of incision?al pain, intrathecal injection of naloxone at 1 ng/kg can inhibit the down-regulation of blood motillin caused by morphine and fentanyl, and which can up-regulate the PWTL, enhancing the analgesic effects of opioids.
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ObjectiveTo study the effects of intrathecal injection of CaMK Ⅱ inhibitor KN93 on the hyperalgesia induced by remifentanil in a incision pain model.MethodsSixty SD rats were divided randomly into 5 groups ( n =12):C group (control) ; (I) group ( incision pain ) ; R group ( incision pain + remifentanil ) ; DMSO group ( incision pain + remifentanil + DMSO) and KN93 group ( incision pain + remifentanil).In group R,DMSO and KN93,remifentanil (0.04 mg/kg,1 mg remifentanil was dissolved in 40 ml NS ) needed to be infused subcutaneously 30 min at the moment of surgery.Group DMSO and group KN93 were respectively intrathecal injected 20 μl DMSO( 10％ ) and 20 μl KN93 (50 μg/20 μl,dissolved in 10％ DMSO).Each rat received tests of the paw mechanical withdrawal threshold (PMWT) and the paw withdrawal thermal latency (PWTL) at the times of 24 h before and 2h,6h,24h,48h after surgery.ResultsCompared with the group C,the PWTL( ( 11.24 ± 0.69) s,(10.36 ±0.29)s,(11.29 ±1.12)s,(12.21 ±0.75)s) and PMWT( (25.5 ± 1.20)s,(24.92 ± 1.98)s,(25.47± 1.54 ) s,( 27.14 ± 1.04 ) s) of the group I were significantly decreased after surgery (P ＜ 0.05 ).Compared with the group Ⅰ,the PWTL( (8.48 ±0.72)s,(8.58 ±0.45)s,(8.46 ±0.92)s,(9.07±0.79) s and PMWT( (21.2± 2.42 ) s,( 19.58 ± 1.12 ) s,( 21.87 ± 1.56 ) s,( 22.26 ± 1.64 ) s ) of the group R were significantly decreased after surgery (P ＜ 0.05 ).Compared with the group R,the PWTL( ( 13.32 ± 0.73 ) s,( 11.79 ± 0.32) s,( 11.86 ±0.98)s,(12.76 ±0.82)s) and PMWT((29.75 ±1.38)s,(28.27± 1.16)s,(26.5 ± 1.02)s,(27.79 ± 1.22)s) of the group KN93 were significantly increased (P ＜ 0.05 ).ConclusionIntrathecal injection KN93 could relieve the hyperalgesia induced by remifentanil
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El dolor agudo postoperatorio constituye un importante desafío para el anestesiólogo y un derecho para los pacientes. No obstante, en la actualidad éste continúa presente en un alto porcentaje de pacientes, a pesar de los esfuerzoz en la difusión de su evaluación y en el uso de diferentes terapias. una importante e interesante forma de cambiar estas cifras puede ser la investigación de la fisiopatología del dolor agudo postoperatorio y la difusión de los resultados. En los últimos años se ha profundizado en el conocimiento de la fisiopatología del dolor agudo postoperatorio, donde se ha determinado que existen cambios capaces de enfrentar la noxa quirúrgica, conocidos como neuroplasticidad, una de cuyas principales expresiones es el mecanismo de sensibilización. Se presenta a continuación una revisión de los principales mecanismos involucrados en el desarrollo y mantención de esta neuroplasticidad.
Accute postoperative pain is a great challenge for anesthesiologists and a right for patients. However, there is still an important percentage of patients with accute postoperative pain, despite all the efforts that have been made to divulge the existing evaluation methods and the use of different therapies. Research of physiopathology of accute postoperative pain might be a relevant and interesting way to change such percentage as well as the publication of the results from that research. In the last years, researchers have gained deeper knowledge in the field of physiopathology of accute postoperative pain and found there are some changes with the capacity to face the surgical noxa known as neuroplasticity, being one of the most important expressions the sensitizazation mechanism. A review of the most important mechanisms that play a part in the development and maintenance of this neuroplasticity is presented below.
Subject(s)
Humans , Male , Female , Pain, Postoperative/physiopathology , Neuronal Plasticity , Neuronal Plasticity/physiology , Synaptic Transmission , Synaptic Transmission/physiology , Posterior Horn Cells/physiology , Posterior Horn Cells/physiopathology , Posterior Horn Cells/chemistry , Microglia/physiology , Microglia/chemistry , Neurons , Neurons/ultrastructure , Afferent Pathways , Afferent Pathways/physiopathology , Afferent Pathways/injuriesABSTRACT
BACKGROUND: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. METHODS: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. RESULTS: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. CONCLUSIONS: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.
Subject(s)
Animals , Rats , Calcium Channel Blockers , Calcium Channels , Calcium , Ethosuximide , Injections, Spinal , Mibefradil , Models, Animal , Nociceptors , Pain, Postoperative , Plastics , Spinal CordABSTRACT
BACKGROUND: Not many recent studies have shown that morphine antinociception may be directly expressed in forebrain structures. It is generally accepted that c-fos is a marker of neuronal activity and its expresson is correlated with nerve pathway activated by nociceptive stimuli. The aim of this study is to examine the effect of morphine on c-fos expression in the incisional pain rat brain. METHODS: A 1 cm longitudinal incision was made through the skin, fascia and muscle of the plantar aspect of the hindpaw in enflurane-anesthetized rats. 10 mg/kg of morphine was injected intraperitoneally 1 hour before (pre-morphine group; n = 15) and 30 minutes after surgery (post-morphine group; n = 15). The same amount of saline was injected 30 minutes after surgery (control group; n = 15). Two hours later c-fos protein expressions in the thalamus, hypothalamus, cerebral cortex and amygdala were examined by immunohistochemistry using a specific antibody. RESULTS: Numerous c-fos positive cells were observed in thalamus, hypothalamus, cerebral cortex, and amygdala in all groups. There were no significant differences in c-fos expression between pre-morphine, post-morphine and control group (P <0.05). CONCLUSIONS: In this study we expected to decreased c-fos expression in incisional pain rat brain by morphine injection. But no differences were observed compared to control group in thalamus and cortex which transmitting pain to CNS, also in hypothalamus and amygdale which transmitting emotional stress to CNS. These results suggests that intraperitoneal morphine can not protect the c-fos expression of ascending pathway to thalamus, hypothalmus, amygdala and cerebral cortex. Also we can not support the effect of morphine on the descending pathway of pain. So we thought for the more information, additional study, for example, behavior test, PCR (polymerase chain reaction)study, may be needed.